ANS effectors Flashcards
Agonist activation of the parasympathetic nervous system has what effect on the salivary glands, heart, airways, GI tract and bladder respectively?
Salivation, reduced heartrate, bronchoconstriction and mucus secretion, increased motility and secretion, relaxation of sphincter and micturition.
What nerve carries parasympathetic innervation to the heart?
Vagus (X)
Which part of the ANS has the longest pre-ganglionic neuron?
Parasympathetic
True or false: the sympathetic postganglionic neurons are longer than parasympathetic
True
What are the acetylcholine receptors on the proximal end of the post-ganglionic neuron in the ganglion called?
Nicotinic
Where are the muscarinic acetylcholine receptors located?
At the target organ.
What type of receptors are nicotinic?
ligand-gated ion channel
What happens to acetylcholine after it has bound to muscarinic receptors at the target organ?
It is hydrolysed by acetylcholine-esterase and choline is transported back into the post-ganglionic nerve to be remade into acetylcholine.
What type of receptors are muscarinic?
G-protein coupled
Where are the G-proteins bonded in the receptor?
To the intracellular surface of the receptor
What are the three types of G protein found in GPCRs?
Gq, Gs and Gi
Describe the sequence of events after acetylcholine has stimulated a GPCR with a Gq protein at the target organ?
Seven subunits of the extracellular receptor change shape, releasing the intracellular Gq protein. This activates phospholipase C which converts PIP2 to IP3. IP3 binds to receptors on the sarcoplasmic reticulum which then releases calcium.
What are the muscarinic antagonists?
aTROPine, ipraTROPium, tioTROPium
Why does atropine have so many undesired side effects?
It is uncharged, so moves across membranes easily and can cause effects on muscarinic receptors all over the body.
What is the difference between ipratropium and tiotropium?
ipratropium is fast-acting for a short duration, tiotropium is slow-acting over a long duration.
What type of receptors would you find at the proximal end of the post-ganglionic fibres in the sympathetic nerve system?
Nicotinic
What part of the ANS are adrenergic receptors found, where specifically are they?
Sympathetic, on the target organ
What neurotransmitter stimulates adrenergic receptors?
Noradrenaline
What tissues receive sympathetic innervation from acetylcholine instead of noradrenaline?
Sweat glands and adrenal medulla
What are the subtypes of adrenergic receptors and why are they different?
Alpha-1 and 2, Beta-1 and 2. They react to adrenaline, isoprenaline and noradrenaline differently. Generally, alpha are more reactive to adrenaline and beta are more reactive to isoprenaline.
What main type of adrenergic receptors are found in the heart and the lungs respectively?
Beta-1- heart
Beta 2- lungs
What type of receptor is an adrenergic receptor?
GPCR (Gs type)
What is the signalling molecule in Gs GPCRs?
cAMP
An influx of sodium into a cardiac cell has what effect?
Increased rate of contraction
An influx of calcium into a cardiac cell has what effect?
Increased force of contraction
What type of drug is salbutamol?
Selective Beta-2 agonist
What is the difference between salbutamol and salmeterol?
Salmeterol has a longer chain that is resistant to breakdown, so has a longer mechanism of action
How id noradrenaline removed from the synapse and what drugs inhibit this?
Via noradrenaline transporter protein, cocaine and amphetamines.
What effects can cocaine have on the heart and bladder?
Increase force and rate of heartbeat, decrease micturition.
What is a LABA?
Long-acting beta-2 agonists
What is the most common side effect of a beta-2 agonist?
Skeletal muscle tremor
What is a common side effect of ipratropium and why?
dry mouth, muscarinic antagonist so decreases salivation
What is the mechanism of action of theophylline?
Inhibits the enzyme the hydrolyses cAMP, meaning cAMP can trigger MLCK to relax smooth muscle (bronchodilation)
What drug class is theophylline in?
Methylxanthines
Methylxanthines are in the same chemical class as caffeine, what does this mean for the side-effects of methylxanthines?
CNS stimulation, heart palpitations
Name an example of a leukotriene antagonist and it’s effects
Montelukast, blocks leukotrienes which are pro-inflammatory mediators, decrease bronchoconstriction, vascular permeability and mucus production
Name two corticosteroids
Prednisolone and beclomethasone
What is different about the mechanism of action of corticosteroids compared to other respiratory medicines?
Bind to cytoplasmic receptors inside cells, they then alter DNA transcription to decrease the production of pro-inflammatory mediators
What are the undesired side effects of corticosteroids?
Adrenal suppression, osteoporosis, Cushing’s syndrome, suppression of immune system.
What is the most common undesired side effect of inhaled corticosteroids?
Oral thrush
Action at what receptors causes the side effect of sedation?
Histamine
Action at dopamine receptors causes what side effects?
Sexual dysfunction and breast changes
What type of G protein is an adrenergic receptor?
Gs
What type of G protein is a muscarinic receptor?
Gq
Describe the mechanism of a Gq receptor
Gq activated by acetylcholine -> phospholipase C converts PIP2 to IP3 -> IP3 binds to receptors on sarcoplasmic reticulum -> calcium released -> MLCK activated -> muscle contraction
Describe the mechanism of a Gs receptor
Gs activated by noradrenaline -> cAMP activated -> increase in Na influx + activates PKA -> increase Ca influx -> increase in force and rate of muscle contraction
